PDBsum entry 3ew3

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protein Protein-protein interface(s) links
Hormone/hormone receptor PDB id
Protein chains
185 a.a. *
203 a.a. *
181 a.a. *
* Residue conservation analysis
PDB id:
Name: Hormone/hormone receptor
Title: The 1:2 complex between a nterminal elongated prolactin and cellular domain of the rat prolactin receptor
Structure: Prolactin. Chain: a. Fragment: unp residues 43-227. Synonym: prl. Engineered: yes. Prolactin receptor. Chain: b, c. Fragment: extracellular domain. Synonym: prl-r, lactogen receptor.
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: prl. Expressed in: escherichia coli. Expression_system_taxid: 562. Rattus norvegicus. Rat. Organism_taxid: 10116.
3.80Å     R-factor:   0.256     R-free:   0.324
Authors: I.Broutin,J.B.Jomain,P.England,V.Goffin
Key ref: I.Broutin et al. (2010). Crystal structure of an affinity-matured prolactin complexed to its dimerized receptor reveals the topology of hormone binding site 2. J Biol Chem, 285, 8422-8433. PubMed id: 20053995
14-Oct-08     Release date:   03-Nov-09    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P01236  (PRL_HUMAN) -  Prolactin
227 a.a.
185 a.a.*
Protein chain
Pfam   ArchSchema ?
P05710  (PRLR_RAT) -  Prolactin receptor
610 a.a.
203 a.a.*
Protein chain
No UniProt id for this chain
Struc: 181 a.a.
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 12 residue positions (black crosses)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     extracellular region   2 terms 
  Biological process     cell proliferation   7 terms 
  Biochemical function     protein binding     4 terms  


J Biol Chem 285:8422-8433 (2010)
PubMed id: 20053995  
Crystal structure of an affinity-matured prolactin complexed to its dimerized receptor reveals the topology of hormone binding site 2.
I.Broutin, J.B.Jomain, E.Tallet, J.van Agthoven, B.Raynal, S.Hoos, B.B.Kragelund, P.A.Kelly, A.Ducruix, P.England, V.Goffin.
We report the first crystal structure of a 1:2 hormone.receptor complex that involves prolactin (PRL) as the ligand, at 3.8-A resolution. Stable ternary complexes were obtained by generating affinity-matured PRL variants harboring an N-terminal tail from ovine placental lactogen, a closely related PRL receptor (PRLR) ligand. This structure allows one to draw up an exhaustive inventory of the residues involved at the PRL.PRLR site 2 interface, consistent with all previously reported site-directed mutagenesis data. We propose, with this description, an interaction model involving three structural components of PRL site 2 ("three-pin plug"): the conserved glycine 129 of helix alpha3, the hydrogen bond network involving surrounding residues (glycine cavity), and the N terminus. The model provides a molecular basis for the properties of the different PRL analogs designed to date, including PRLR antagonists. Finally, comparison of our 1:2 PRL.PRLR(2) structure with those of free PRL and its 1:1 complex indicates that the structure of PRL undergoes significant changes when binding the first, but not the second receptor. This suggests that the second PRLR moiety adapts to the 1:1 complex rather than the opposite. In conclusion, this structure will be a useful guiding tool for further investigations of the molecular mechanisms involved in PRLR dimerization and activation, as well as for the optimization of PRLR antagonists, an emerging class of compounds with high therapeutic potential against breast and prostate cancer.

Literature references that cite this PDB file's key reference

  PubMed id Reference
20846877 E.M.Jacobson, E.R.Hugo, T.R.Tuttle, R.Papoian, and N.Ben-Jonathan (2010).
Unexploited therapies in breast and prostate cancer: blockade of the prolactin receptor.
  Trends Endocrinol Metab, 21, 691-698.  
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